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Biomedical subjects

N Wright

Publications and source records attributed to N Wright.

At least 55 records · Page 3Linked to original sources

Dynamics of risk behavior for HIV infection among young Thai men.

The objective of this investigation was to analyze the dynamics of risk for HIV-1 infection among young men in Thailand. We conducted a prospective study in a cohort (n = 1,236) of young men, aged 19-23 years at conscription into the Royal Thai Army and Air Force from six provinces in northern Thailand in May 1991 who were followed until their discharge in April 1993. The outcome measure was change since conscription in the frequency of self-reported sex with female commercial sex workers (CSW) during military service. Although 42% of conscripts reported no visit to a female CSW in the year prior to conscription, most had a visit during military service. Men who visited female CSWs infrequently at baseline increased their visits somewhat over time, whereas those with high initial rates of CSW visits decreased. Based on an assumed stable distribution over time, change from baseline was not statistically significant. Only marital status and high baseline CSW visit rates were associated with diminished visit frequency in multivariate analysis. No differences were seen in patterns of change in CSW visits by HIV-1 serostatus. More aggressive preventive interventions are needed to reduce the frequency of CSW visits in northern Thailand, a setting where 40-80% of all female CSWs working in brothels are now HIV seropositive.

Adult↗

Automatism re-visited: post-traumatic automatism as a defence to a serious criminal charge.

A case is described of a policeman who assaulted the man he was arresting after receiving a concussive blow to the head. The defence argued he was suffering from post-traumatic automatism and after juries were unable to agree a verdict in two trials he was acquitted. Aspects of post-traumatic automatism in English law are described and theories of the neurology of concussion and aggressive behaviour are discussed. Guidelines are proposed for the evaluation of cases of post-traumatic automatism.

Automatism↗

Trefoil peptides. Coming up clover.

Now that information on trefoil domain structure is available from X-ray crystallographic and nuclear magnetic resonance spectroscopy studies, we can begin to understand the functions of these unusual protein motifs.

Amino Acid Sequence↗

Seroprevalence of HIV antibodies and risk factors in healthy young males from upper north Thailand.

In the Spring of 1991 a random sample of young men from Upper Northern Thailand (mean age = 21 years) was interviewed by trained medical students from Chiang Mai University, serum samples were obtained and analyzed for prevalence of HIV-1 antibodies and for syphilis, and risk factors for HIV infection were assessed. It was found that Commercial Sex Workers (CSW) were the principal risk factor, that consistent condom use is rare, and the rates of HIV infection are rising rapidly. Sociodemographic background, homosexual behavior, drug use, and history of STD's were found to be not significant risk factors. The conclusions are that the education campaigns should be intensified to reduce the frequency of contact with CSW and to encourage consistent use of condoms.

Adult↗

Risk factors for HIV infection among young adult men in northern Thailand.

OBJECTIVE: To determine the sociodemographic and behavioral risk factors associated with human immunodeficiency virus (HIV) infection in two cohorts of young men selected for military service in northern Thailand. DESIGN: Military conscripts were studied cross-sectionally after conscription in May 1991 and November 1991. Risk factors were assessed by interview with trained nonmilitary interviewers. SETTING: Two military training bases in Chiang Mai, Thailand. PARTICIPANTS: A total of 2417 young men aged 19 to 23 years (mean age, 21 years) conscripted by lottery into military service in the Royal Thai Army or Royal Thai Air Force from six provinces in northern Thailand. MAIN OUTCOME MEASURES: Human immunodeficiency virus seroprevalence by enzyme-linked immunosorbent assay confirmed by Western blot and univariate and multivariate analyses of sociodemographic and behavioral risk factors associated with HIV seroprevalence. RESULTS: Overall, 289 (12.0%) of 2417 men were HIV-seropositive at baseline. The strongest associations with being HIV positive were heterosexual activities. History of sex with a female commercial sex worker (CSW) was frequent (96.5% of men who were HIV-positive and 79.0% of men who were HIV-negative) and strongly associated with HIV infection on univariate and multivariate analyses (adjusted odds ratio, 1.60 to 2.07, depending on the frequency of CSW contact). Also, sexually transmitted diseases were common and associated with HIV infection in both univariate and multivariate analyses (adjusted odds ratio, 3.36). Sex with other males and injection drug use were uncommon and not associated with HIV infection. Condom use was reported in 61.5% of men at last sex with a CSW but was not shown to be protective of prevalent HIV infection. CONCLUSION: The epidemic of HIV infection has spread widely among young men in northern Thailand, despite reported frequent and recent use of condoms during sex with female CSWs. Control of HIV infection in this population will probably require more regular and effective use of condoms, prevention and treatment of sexually transmitted diseases, and reduction in the frequency of CSW contact.

Adult↗

Report of the Canadian Hypertension Society Consensus Conference: 2. Diagnosis of hypertension in adults.

OBJECTIVE: To update recommendations for the diagnosis of mild hypertension in adults and to assess the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring. DATA SOURCES: Literature reviews of previous consensus conferences were updated with searches of MEDLINE for the period Jan. 1, 1988, to Nov. 15, 1991, and supplemented by reference lists and personal files. STUDY SELECTION: Panel members selected relevant articles and rated them according to methodologic criteria. DATA EXTRACTION: The data extracted concerned the measurement of blood pressure, the diagnosis of hypertension, the treatment of mild hypertension, and the reliability and validity of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring in the diagnosis of mild hypertension. The recommendations made were graded according to the level of evidence available, circulated to many experts and approved at a consensus conference. MAIN RESULTS: Previous recommendations for the accurate measurement of blood pressure remain mostly unchanged. Antihypertensive treatment should be prescribed for patients (including the elderly) with an average diastolic blood pressure of at least 100 mm Hg, for those with isolated systolic hypertension (systolic blood pressure of at least 160 mm Hg and diastolic blood pressure of less than 90 mm Hg) and for patients with a diastolic blood pressure of 90 to 99 mm Hg and target-organ damage. Clinical judgement is required in treating patients with a diastolic blood pressure of 90 to 99 mm Hg without target-organ damage, and individual risk for cardiovascular disease must be taken into account. There is insufficient evidence to warrant the routine use of echocardiography, self-measurement of blood pressure or ambulatory blood pressure monitoring in diagnosis. CONCLUSIONS: Recent high-quality evidence supports several new recommendations for the diagnosis of mild hypertension in adults. Additional research is needed to determine the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring.

Adult↗

Treatment of hyperlipidemia in the nephrotic syndrome: the effects of pravastatin therapy.

The hyperlipidemia of the nephrotic syndrome is characterized by an elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), with a normal or low high-density lipoprotein cholesterol (HDLC), and an increase in triglycerides (TGs) later in the course of the disease. If sustained, this lipid profile probably places these patients at increased risk for cardiovascular disease. Despite extensive trials of diet and drug therapy in patients with primary hyperlipidemias, few such trials exist in patients with the nephrotic syndrome. We conducted a randomized, prospective, double-blind, placebo-controlled trial to investigate the efficacy and safety of pravastatin, the newest cholesterol synthesis inhibitor, in the treatment of the hyperlipidemia of the nephrotic syndrome. After dietary modification was implemented, 13 patients received pravastatin and eight received placebo. All patients were maintained on a low-fat, low-cholesterol diet for the duration of the trial (24 weeks). The dose of pravastatin was increased from the initial 20 mg/d to 40 mg/d at week 10 or 18 if TC remained elevated (> 50th percentile). A bile acid sequestrant was added at week 18 if TC remained elevated and if the patient was already receiving the maximal pravastatin dosage. Dietary modification did not significantly change the lipid profile. Pravastatin (20 mg/d) reduced TC by 22% from a baseline of 301 +/- 28 mg/dL (P < 0.05) and LDLC by 28% from a baseline of 222 +/- 28 mg/dL (P < 0.05). When used at 40 mg/d (in six patients) no further change in the lipid profile was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Behavioral and sociodemographic risks for frequent visits to commercial sex workers among northern Thai men.

OBJECTIVE: The transmission of HIV-1 in Thailand has recently been attributed to exposure to infected commercial sex workers (CSW). We sought to identify risk factors for patterns of CSW visits among northern Thai men. DESIGN: Retrospective recall of lifetime and recent CSW visits and associated risk factors were obtained by interview. SETTING: Two military bases in northern Thailand. PARTICIPANTS: We enrolled two cohorts (n = 2417) of young men, aged 19-23 years, who were conscripted into the Royal Thai Army and Air Force from six provinces in northern Thailand in May and November 1991. MAIN OUTCOME MEASURES: Frequency of self-reported lifetime and recent sex with CSW. RESULTS: Multivariate results showed that lower socioeconomic status, early first intercourse and substance-use factors (alcohol, marijuana, other drugs, and smoking) associated with lifetime and recent sex with CSW. Sexual intercourse with other female partners, lower price paid at last CSW visit and frequency of condom use with CSW did not differentiate frequent from infrequent CSW visitors. CONCLUSIONS: Limits in the frequency of sex with CSW, improved condom practices and reduction of drinking prior to CSW visits would all appear to provide substantial protection from exposure to HIV-1 in this setting.

Adult↗

An approach to consumer feedback in an out-patient specialty service.

Details an approach to consumer feedback in an out-patient specialty service. Outlines the approach to undertaking a consumer survey and how feedback from people using the Genito-Urinary Medicine services can be obtained. The aim of the survey was to assess the level of individual/personal care. Gives the objectives and methodology, main findings and recommendations, together with a cost benefit analysis of the work.

Costs and Cost Analysis↗

Trefoil peptide expression in intestinal adaptation and renewal.

There are many avenues where molecular biology is important in studying the gut, and here we explore methods for defining expression of a new gene family in the gut. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide mRNA and peptide are expressed in the acinar and proximal duct cells, whereas pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed ectopically by goblet cells. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules. pS2 peptide was demonstrated in local neuroendocrine cells and was also co-packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We have also cloned the newest trefoil peptide intestinal trefoil factor from human and rat intestinal mucosa and shown its co-expression with mucus by normal intestinal goblet cells. The co-packaging of the same secretory protein in both mucous and neuroendocrine granules, which have different functions, is unusual and indicates an important role for pS2 in the secretory process itself or as a ligand delivered to its receptor via multiple routes. We conclude that the trefoil peptides are widely distributed in the intestine in inflammatory bowel disease and are of considerable potential functional importance.

Amino Acid Sequence↗

Glycine toxicokinetics: vitreous fluid concentration and visual impairment.

We report the results of kinetic experiments in sheep. Following systemic loading with 45 g glycine, plasma, cerebral spinal fluid (CSF), and vitreous fluid from the vitreous body of the eye were assayed for glycine concentrations. Mean baseline plasma, CSF, and vitreous glycine concentrations were 730, 46, and 191 mumol/L respectively. One hour after loading, values were 21292, 1103, and 1150 mumol/L respectively. During the succeeding 7 h plasma and CSF concentrations fell in parallel but remained above normal. In contrast the vitreous concentrations remained high and did not change significantly during the 7 h post-infusion period. Retinal glycine receptors may be particularly vulnerable to neurotoxic effects of glycine because of these pharmacokinetic properties.

Animals↗

Bronchoalveolar lavage in the prediction of post-thoracotomy chest infection.

A prospective study was carried out on 75 patients undergoing pulmonary surgery to determine the relationship between perioperative lung flora and postoperative infections. Seventy-five patients having pleurectomy or pneumonectomy received cefuroxime prophylaxis; 1.5 g i.v. at induction followed by 6 further doses of 0.75 g i.v. over 48 h. Bronchoalveolar lavage samples were taken perioperatively via bronchoscopy in pleurectomy patients and from excised lung in patients undergoing lung resection. Patients were monitored for development of chest infection during the first 10 days after operation. Bacterial pathogens were cultured from 12 out of 54 lavage samples. The most common pathogen was Haemophilus influenzae and all the organisms were sensitive to cefuroxime. Eight patients (10.7%) developed postoperative chest infection. The likelihood of developing postoperative chest infection was 42% (5 out of 12 patients) in those patients whose lavage culture was positive for bacterial pathogens compared to 4.8% (2 out of 42 patients) for those whose culture was negative (chi 2 test, p less than 0.001). These results suggest that the culturing of bacterial pathogens from lavage samples from resected lung is a significant predictor of postoperative chest infection in patients undergoing pulmonary resection.

Bronchoalveolar Lavage Fluid↗

Juvenile GM2 gangliosidosis caused by substitution of histidine for arginine at position 499 or 504 of the alpha-subunit of beta-hexosaminidase.

Juvenile GM2 gangliosidosis is a rare neurodegenerative disorder closely related to Tay-Sachs disease but of later onset and more protracted course. The biochemical defect lies in the alpha-subunit of the lysosomal enzyme beta-hexosaminidase. Cultured fibroblasts derived from patient A synthesized an alpha-subunit which could acquire mannose 6-phosphate and be secreted, but which failed to associate with the beta-subunit to form the enzymatically active heterodimer. By contrast, fibroblasts from patient B synthesized an alpha-subunit that was retained in the endoplasmic reticulum. To identify the molecular basis of the disorder, RNA from fibroblasts of these two patients was reverse-transcribed, and the cDNA encoding the alpha-subunit of beta-hexosaminidase was amplified by the polymerase chain reaction (PCR) in four overlapping fragments. The PCR fragments were subcloned and shown by sequence analysis to contain a G to A transition corresponding to substitution of histidine for arginine at position 504 in the case of patient A and at position 499 in the case of patient B. The mutations were confirmed by hybridization of allele-specific oligonucleotides to PCR-amplified fragments of DNA corresponding to exon 13 of the alpha-subunit gene. The Arg504----His mutation was found on both alleles of patient A as well as of another unrelated patient; the homozygosity of this mutant allele is attributable to consanguinity in the two families. The Arg499----His mutation was found in patient B in compound heterozygosity with a common infantile Tay-Sachs allele. There is additional heterogeneity in juvenile GM2 gangliosidosis, as neither mutation was found in the DNA of a fourth patient. The Arg----His mutations at positions 499 and 504 are located at CpG dinucleotides, which are known to be mutagenic "hot spots."

Arginine↗

Swing-through vs. reciprocating gait patterns in patients with thoracic-level spina bifida.

Three thoracic level spina bifida patients were evaluated in a gait laboratory. The patients first were asked to walk with a swing-through gait pattern using conventional hip-knee-ankle-foot orthosis and then with a reciprocating gait pattern using the reciprocating gait orthosis (RGO). The reciprocating gait was modestly more efficient than the swing-through gait pattern. The average speed of free walking was 11.4 meters per minute with the swing-through pattern and 16.2 meters per minute with the reciprocating pattern. The stride length was 0.31 meters and 0.54 meters with the swing-through and reciprocating patterns respectively. The RGO needs further modifications to improve the walking ability of spina bifida patients. The hip joints permit only flexion and extension and no rotational movement. The lack of internal and external rotation inhibits hip movement, reduces stride length, reduces the speed of walking and causes the cables to bind and eventually break. With design changes, future bracing systems will permit improved walking in the high level spina bifida patients.

Braces↗

The effect of lithium on pupillary response to pulses of light in sheep.

Administration of lithium carbonate to sheep in the dose range of 600-1800 mg/day resulted in a linearly described rise in lithium levels in plasma and red blood cells. In contrast to the rodent model but in agreement with the human condition, plasma lithium levels exceeded those of red blood cells. Polydipsia and body weight changes were not evident. At plasma levels of 0.70-0.8 mM/l, lithium attenuated the ability of the pupil to constrict in response to 30-sec pulses of light in the 25-150 microW/cm2 intensity range but not the ability to dilate in the dark. Thus, similar to observations in normal human volunteers and bipolar patients, lithium reduces sensitivity to light. The sheep is proposed as a useful model for studying the actions of lithium.

Animals↗

Glycine inhibition of pupillary responses to pulses of light in conscious sheep.

The use of a 1.5% glycine solution as a bladder irrigant during surgical removal of the prostate has been associated with transient visual impairment. Glycine is thought to be an inhibitory retinal transmitter. Adult female sheep were infused with a 1.5% glycine solution to provide a dose of 0, 7.5, 15, 30, or 60 g of glycine. The volume control was a solution of dextrose and saline. The degree of constriction of the pupil in response to 30 seconds of bright light following dilation in the dark was used as an index of visual response. Observations were made before and 2, 4, 6, 12, 24, 48, 96, and 192 hours after a single infusion. Significant inhibition of pupil response to light but not to the dark was apparent following systemically administered glycine resulting in plasma levels over 5000 mumol/L. Inhibition of pupil response was paralleled by behavioral indices of visual impairment but not by changes in plasma sodium, potassium, chloride or osmolality. The duration of the effect was dose dependent with visual impairment following a single high dose of glycine being detectable five days later and long after glycine levels had returned to normal. However, the relationship between dose, time, and effect appears to be complex. It is important to note that the present observations occurred at plasma glycine levels frequently experienced in routine surgical practice. The finding that significant long term detrimental effects of glycine could be detected should evoke a re-evaluation of the use of glycine as an irrigating solution for surgical procedures and stimulate further investigation of the effects of glycine on retinal function and the ability to perceive light.

Animals↗

Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis (CAPD).

Ten adult patients on continuous ambulatory peritoneal dialysis (CAPD) received one dose of trimethoprim-320 mg (TMP) and sulfamethoxazole 1600 mg (SMX) orally (p.o.), intravenously (i.v.), and intraperitoneally (i.p.) on three separate occasions to characterize the pharmacokinetics of both drugs. Concentrations of both TMP and SMX were measured in serum and dialysate by HPLC to 48 h. Half-life, total body clearance (TBC), and peritoneal clearance (PCl) were determined. The mean half-life of TMP was 28 h, while for SMX it was 12.5 h. Relative to the i.v. dose, the bioavailability following oral administration for TMP was 98% and 87% for SMX. Intraperitoneal bioavailability was 73% for TMP and 65% for SMX after a 4-h dwell. After 24 h, regardless of the route of administration, less than 3% of TMP and less than 6% of SMX appeared in dialysate. We conclude that peritoneal losses contribute insignificantly to TMP/SMX elimination during CAPD.

Administration, Oral↗